Chemoprevention of azoxymethane-induced colon carcinogenesis by delta-tocotrienol

Kazim Husain, Anying Zhang, Steve Shivers, Ashley Davis-Yadley, Domenico Coppola, Chung Yang, Mokenge P. Malafa

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Abstract

This study evaluated the preclinical activity of dtocotrienol (DT3), a bioactive form of vitamin E, in the inhibition of colorectal cancer growth and development in vitro and in vivo. DT3 is the most bioactive isomer of vitamin E in inhibiting growth of colorectal cancer cells. However, it had little effect on the proliferation of normal colon mucosal cells NCM460. In HCT-116 and SW-620 colorectal cancer cells, DT3 (50 mmol/L) significantly inhibited malignant transformation (P < 0.02, P < 0.001), cell migration (P < 0.02, P < 0.05), and invasion (P < 0.05, P < 0.01) compared with vehicle. DT3 inhibited markers for epithelial (E-cadherin) to mesenchymal (vimentin) transition, metastasis (matrix metalloproteinase 9), angiogenesis VEGF, inflammation (NF-kB), and Wnt signaling (b-catenin) compared with vehicle in colorectal cancer cells. DT3 induced apoptosis selectively in colorectal cancer cells (SW-620 cells, HCT-116 cells, and HT-29) without affecting the normal colon cells. In the azoxymethaneinduced colorectal carcinogenesis model in rats, DT3 (200 mg/kg orally twice a day) for 20 weeks significantly inhibited colorectal polyps by 70% and colorectal cancer by almost 99% compared with the vehicle treatment group (P < 0.02, P < 0.001), and the cancer inhibition effect was more potent than sulindac (50%). Taken together, these data demonstrate that DT3 is a potential chemopreventive agent in colorectal cancer, warranting further investigation into its clinical use in the prevention and treatment of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)357-366
Number of pages10
JournalCancer Prevention Research
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Husain, K., Zhang, A., Shivers, S., Davis-Yadley, A., Coppola, D., Yang, C., & Malafa, M. P. (2019). Chemoprevention of azoxymethane-induced colon carcinogenesis by delta-tocotrienol. Cancer Prevention Research, 12(6), 357-366. https://doi.org/10.1158/1940-6207.CAPR-18-0290